This will be a trial to test the clinical and radiographic efficacy of monthly pulse infusion therapy in beta-interferon-resistant active MS patients. While beta-interferon medications have been shown to reduce disease activity in relapsing remitting MS patients, many patients continue to have active disease despite being on these medications. There is evidence that treatment of these patients with pulse methylprednisolone, pulse mitoxantrone or pulse cyclophosphamide may effectively reduce disease activity in these patients and potentially allow them to be stable maintained on beta-interferon therapy thereafter. This study is designed to randomize beta-interferon non-responsive patients for six months of treatment to either monthly intravenous pulse cyclophosphamide plus methylprednisolone or monthly intravenous pulse mitoxantrone plus methylprednisolone or monthly intravenous methylprednisolone alone. Patients will be maintained on beta-interferon and followed over 24 months. 20 patients will be enrolled per arm. MRI number of gadolinium enhancing lesions and T2 lesion volume will be the principal outcome measures while clinical scores and immunologic studies will be secondary outcome measures. Measurement of adverse events will also be an important component. Thus far the applicant's research has focused on immunologic studies in MS with the goal of understanding the mechanism of action of drugs used to treat the disease. We have found that the treatment of MS patients with some of these agents results in a number of changes, notably increases of IL-4 secretion associated with eosinophilia and decreases in IL-12.